The newborn is acutely susceptible to gastrointestinal (GI) infections by Salmonella, which often progress to disseminated systemic disease. To reveal age and dosage-related features of Salmonella infections in a young mouse model we used a noninvasive method of monitoring bacterial infections in living animals. A virulent Salmonella strain expressing luciferase from Photorhabdus luminescens was grown in static culture and diluted to approximately 2 bacteria/μl as determined by colony forming units (cfu). Groups of BALB/c mice aged 1-6 weeks were infected orally with 6 μl, 12 -15 cfu. Bioluminescence produced by the bacteria was transmitted through the living tissues and detected noninvasively over time. Animals were examined daily over 7 days for bioluminescence using an intensified CCD camera. One and 2 week old mice demonstrated GI infections at 24 h post infection (p.i.). From 4-7 days p.i. the patterns of photon emission suggested disseminated infection with involvement of the lungs and lymph nodes. The 4 and 6 week old mice had no detectable photon emission at any time and remained healthy. Two week old mice were also susceptible to strains of Salmonella that demonstrated reduced virulence properties in adult mice (LB5000lux and BJ66lux). To develop a two color assay for GI infection and host response, 2 groups of 4 week old transgenic (Tg) indicator mice were infected orally with either unlabeled or SL1344lux that emit blue light (peak at 490 nm). The indicator gene in the Tg mice consists of the promoter of HIV fused to firefly luciferase. Cells in these mice emit yellow-green light (peak at 560 nm) in response to various stimuli, including lipopolysaccaride, as a marker of host response. Infected animals were followed daily using filters to differentiate the two wavelengths of emission. In infected animals the yellow-green light colocalized with the blue emission. We conclude that Salmonella infection and host response can be monitored noninvasively; young mice are susceptible to low inocula of Salmonella, while older animals are not; and Salmonella strains with reduced virulence can cause serious disease in neonates. Our model will be useful in investigating the role of bacterial genetics and phenotype, as well as host factors in susceptibility to and progression of GI infections.